P369: DONOR-DERIVED ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR T CELLS FOR B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: A PHASE 1 TRIAL
Authors: Yi Luo, Lei Gao, Jia Liu, Luxin Yang, Lu Wang, Xiaoyu Lai, Shichun Gao, Lizhen Liu, Lu Zhao, Yishan Ye, Manning Wang, Shengyu Liao, Lianjun Shen, Wei William Cao, Dongrui Wang, Wenling LI, XI Zhang, He Huang
Journal: HemaSphere (2023)

Background: Autologous chimeric antigen receptor (CAR) T-cell therapy have greatly improved the outcomes of refractory/relapse (r/r) B-cell acute lymphoblastic leukemia (B-ALL). There have been studies showing therapeutic potential of donor-derived CAR T cell therapies in r/r B-ALL patients post allogeneic hematopoietic cell transplant (allo-HSCT). However, clear feasibility and safety of donor-derived CAR T in these patients has yet to be shown. Here, we report the phase 1 results of donor-derived anti-CD19 CAR T cells (GC007g) in r/r B-ALL patients who relapsed from allo-HSCT. Aims: This phase 1 clinical trial (NCT04516551) aims to evaluate safety and efficacy of donor-derived anti-CD19 CAR T cells (GC007g) in B-ALL patients who relapsed after allo-HSCT. Methods: Between 15 March 2021 and 19 May 2022, we administered anti-CD19 CAR T cells which were derived from previous allo-HSCT donors, to patients with r/r B-ALL. Key inclusion criteria included r/r B-ALL patients after allo-HSCT with ECOG≤1 and positive CD19 expression determined by bone marrow flow cytometry. The primary end point was safety with efficacy secondary. Results: Nine patients were enrolled in this study. Six (66.7%) patients relapsed after haploidentical HSCT while three (33.3%) relapsed post matched sibling donors HSCT. The median time from HSCT to relapse was 185 days (range, 81-2,063 d). Upon screening step, patients had a median 82% (6-93%) blast cells in bone marrow. The median age of patients was 31 years (range 21-48), and seven patients (77.8%) had BCR-ABL fusion gene. Donor-derived CAR-T cells were successfully manufactured for all patients, with a median time from leukapheresis to infusion of 33 days (range, 30-74 d). Patients received donor-derived CAR T cells infusions at 6x105/kg (n=3) or 2x106/kg (n=6) dose level. CAR T cells expanded in vivo and the median time to reach maximum CAR T cell expansion (Cmax) was 9 days (range, 7-11) and median Cmax was 54,025 copies/ug gDNA (ranging17,239-490,338). One patient (at 2x106/kg dose level) had hyperbilirubinemia after GC007g infusion which was defined as a dose-limiting toxicity. All patients experienced grade 1-3 CRS, and all resolved after treatment. No immune effector cell associated neurotoxicity syndrome observed. Three patients had acute graft-versus-host-disease (aGvHD) (grade1, n=1; grade 2, n=1; grade 4, n=1), the symptoms of aGvHD occurred at day 3, day5 and day32 post CAR-T infusion respectively and all resolved after standard of care. No chronic graft-versus-host-disease (cGvHD) occurred. All patients experienced grade 3 or higher hematological adverse events. At day 28 after infusion, all patients achieved complete remission with/without incomplete hematologic recovery (CR/CRi) with undetectable MRD. At a median follow-up of 445 days (range 218-649 d), seven patients remained in CR/CRi while two had CD19-negative relapse. The overall response rates (ORR) were 100% (7/7), 85.7% (6/7), and 50% (2/4) at month 3, month 6, and month 12, respectively. CAR copies were still detectable in 75% (6/8) and 67% (4/6) of patients at month 6 and 12, respectively. The 1-year PFS and OS were 76.2% and 85.7%, respectively. Summary/Conclusion: Donor-derived CD19 CAR T-cell expanded and induced durable remission in patients with B-ALL relapsed after allo-HSCT, with manageable safety profiles. Phase 2 clinical trial of GC007g is currently recruiting.Keywords: B cell acute lymphoblastic leukemia, CAR-T